METHODS FOR DEVELOPMENT OF KDIGO CLINICAL PRACTICE GUIDELINES

Topic Selection & Prioritization

 

KDIGO guidelines focus on topics related to the prevention or management of individuals with kidney diseases. The selection of topics for guideline development is a critical component of the guideline development process. Criteria used by KDIGO for topic prioritization include the following:

      • Burden of illness based on prevalence and scope of the condition or clinical problem.
      • Amenability of a particular condition to prevention or treatment and expected impact.
      • Existence of a body of evidence of sufficient breadth and depth to enable the development of evidence-based guidelines.
      • Potential of guidelines to reduce variations in practices, improve health outcomes, or lower treatment costs.

 

Although KDIGO is able to build on a set of guidelines previously developed by other nephrology groups, KDIGO attempts to coordinate the updating of these guidelines and aims to expand the range of topics covered. In the past, input into this process has been solicited from colleagues worldwide through the distribution of questionnaires at international conferences and through the topic proposals on the KDIGO website. Topics are regularly vetted and priorities defined by the KDIGO Executive Committee and Board of Directors. A guideline coordination task force comprising representatives of other organizations that develop English-language clinical practice guidelines for individuals with kidney diseases meets annually to coordinate the guideline development plans of each organization in order to avoid unnecessary duplication of efforts.

 

Controversies Conferences

 

As a precursor to guideline development, KDIGO regularly hosts international Controversies Conferences to summarize the available knowledge in specific topic areas, discuss what kind of recommendations can be derived from the available knowledge, and assess what is needed to improve the evidence base for clinical management.

These conferences help KDIGO to decide whether sufficient evidence is available for the development of a clinical practice guideline in a specific area; if evidence is not sufficient, what research is needed to generate necessary evidence; and when the optimal timing for guideline development might be.

 

Work Group Selection

 

KDIGO guidelines are developed by independent, international, multidisciplinary work groups (WGs) comprising 12–20 members, led by two co-chairs. The WG co-chairs are selected by the KDIGO co-chairs in collaboration with the KDIGO Executive Committee. WG co-chairs are chosen on the basis of their leadership skills and domain expertise and are usually from different continents. One WG co-chair can be selected from outside the direct clinical topic area to facilitate a wider perspective to ensure freedom from any stakes in the topic. WG members are then selected by WG co-chairs, in collaboration with KDIGO co-chairs, taking into consideration the need for:

      • Clinical and technical expertise in the relevant topic areas.
      • Multidisciplinary and multinational membership.
      • Process and methodological expertise.
      • Minimal or no conflicts of interest.

 

The panel of identified WG candidates is then reviewed and approved by the KDIGO Executive Committee. Experts in pediatric nephrology are usually included, as are representatives of relevant non-nephrology disciplines. Some WG members may serve as liaisons to other guideline groups and professional societies to ensure coordination.

 

Averting Conflicts of Interest

 

KDIGO takes active steps to minimize actual or perceived conflicts of interest. Many areas of guideline development involve commercially available products. Experts in the field may have ties with industry that can or can appear to impact their judgments. To avert conflicts of interest interfering with the WG’s appraisals during guideline development, KDIGO follows stringent transparency rules.

At the start of the development process, potential conflicts of interest for a particular guideline are considered, with a goal of appointing WG co-chairs and members that do not have overt conflicts. When appointing members with potential conflicts is deemed necessary to provide particular technical expertise, efforts are made to enlist other members with alternative perspectives. Members with known conflicts are asked to abstain from voting on the guideline recommendations. WG members are periodically required to formally declare relevant financial relationships with commercial entities or other potential conflicts of interest. This information is disseminated within the WG at its meetings. The declarations of WG members are also summarized in each guideline document. In addition, KDIGO contracts with an independent group of methods staff, called the evidence review team (described below), to ensure that pertinent evidence is systematically reviewed and appropriately accounted for. Moreover, KDIGO does not accept direct funding for any guideline project; rather, each project is supported by a consortium of sponsors. Finally, all drafts of KDIGO guidelines are subjected to extensive public review, to enhance openness and transparency.

Finally, members of the KDIGO Board of Directors are also asked to indicate their ties to industry. This information is collated and available for review.

 

Role of the Evidence Review Team

 

A primary principle of KDIGO guideline development is scientific and methodological rigor. KDIGO contracts with an independent professional evidence review team (ERT), which is tasked with providing methodological expertise in guideline development to KDIGO in general and for the individual guideline projects. The ERT at the Tufts Center for Kidney Disease Guideline Development and Implementation, Tufts Medical Center, Boston, MA, USA, consists of a standing staff with expertise in systematic review, meta-analysis, guideline development, clinical research, and clinical nephrology.

The methods employed by the ERT are aligned with the Comparative Effectiveness Review methodology used by the Evidence-based Practice Center (EPC) program of the Agency for Health Care Research and Quality. The ERT shares personnel with the Tufts EPC.

The ERT interacts and collaborates with each WG closely throughout all stages of the guideline development process. The ERT trains the WG and its chairs in the methods of evidence-based guideline development, assists the WG to develop the scope of the guidelines and the systematic reviews of the evidence for each guideline, conducts the systematic reviews, provides interpretation of the quality and relevance of the evidence, guides the WG through the standardized process of guideline development , assists the WG with framing and grading the recommendations, and ensures that the grading is consistent with the evidence and its strength. Since systematic review and evidence-based guideline development requires specific training and expertise and is time-consuming, contracting with an external team accomplishes the evidence reviews in a professional and timely manner with rigorous methodology. While the WG retains ultimate responsibility for the final guideline document, the contribution of the ERT is reflected in its co-authorship for the published guideline documents.

 

Guideline Development Process

 

A guideline is developed over the course of 1.5 to 2 years. During this time, the WG meets in person approximately three times for new guidelines, and twice for guideline updates, and communicates regularly between meetings via teleconferences and email.

A guideline may span many topics. Not all guideline topics are addressed by in-depth evidence review. When the anticipated outcome of an extensive literature search is unlikely to yield evidence that directly informs practice choices, the result may not justify the effort. However, topics that relate to explicit selection of diagnostic tests or interventions are preferentially chosen to undergo systematic review of the best available evidence. This entails a priori question formulation, specification of important outcomes for the review, systematic searches, data extraction, tabulation, analysis, and synthesis of evidence. This standardized process aims to minimize bias in interpretation and facilitates comparison across studies as well as a combined analysis of their findings.

In KDIGO guideline documents, each set of recommendations related to a specific question or topic is followed by a “rationale” section, which summarizes the evidence and the reasoning for each recommendation and explains why specific wording was chosen. Evidence review tables provide details of the design and results of studies that were considered to be relevant for a specific topic.

WGs are asked to highlight areas for future research and outline how to fill important gaps of knowledge. These recommendations for future research are used to set research priorities and to inform selection of research proposals for funding.

KDIGO clinical practice guidelines are intended to provide guidance rather than rules. Although the purpose of the recommendations is to assist in decision making, a guideline recommendation cannot anticipate for all possible variations of patient, provider, and system factors. Thus each provider retains the privilege and responsibility to assess the appropriateness of a particular recommendation in a specific context. Since KDIGO issues “international” guidelines without a concrete setting of reference, it is expected that recommendations may need to be adapted for regional or local context.

 

Evidence Rating

 

Guideline recommendations should be graded to communicate the degree of confidence that following a recommendation will do more good than harm. The grade of a recommendation will depend on the quality of the supporting evidence as well as judgments and preferences regarding the balance of the possible benefits and harms for the recommended practice.

KDIGO follows the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, which has been widely adopted. This approach assigns separate grades for the quality of the evidence and for the strength of the recommendation. The quality of evidence is graded as either high (A), moderate (B), low (C), or very low (D), and the strength of a recommendation as either level 1 (strong) or level 2 (weak or discretionary)(Table 1).

 

Table 1: Quality of Evidence and Strength of Recommendations

Quality of Evidence - Table 1

 

A level 1 grade implies that a recommendation should be followed on the basis of the assumption that a well informed consumer would almost always want to pursue the recommended course of action. By contrast, many patients may want to pursue a level 2 recommendation but a substantial number of patients may not. This means that the risks and benefits must be weighed in each specific situation, taking into account the patient’s preferences and values (Table 2). Level 1 recommendations can be examined to determine their suitability for use in developing a clinical performance measure. On the other hand, a level 2 grade inherently indicates uncertainty, and future research may provide higher quality evidence or more precise estimates or yield opposing findings.

 

Level of Strength

 

Although the higher the quality of the evidence, the higher the likelihood of a strong recommendation being derived, no direct algorithm links the strength of a recommendation to the quality of evidence. The combination of the four levels of evidence quality and the two levels of strength of recommendation allows for considerable granularity. In addition, WGs can choose to make an ungraded statement, particularly for questions that are not suitable for systematic evidence review or if the WG issues general guidance based on common sense without reasonable alternatives.

In the appraisal of evidence and in formulation and grading of a guideline recommendation, judgment and interpretation are unavoidable. Expert opinion is particularly influential when evidence is not conclusive or definitive. In that case, a WG may decide to put forward its best guess or it may refrain from making a recommendation. After extensive research and discussion, the KDIGO Board of Directors has decided to encourage guideline WGs to provide their best possible guidance, even in areas of inconclusive evidence. The decision of whether to do so ultimately rests with the WG. If it decides to do so, the WG needs to designate the recommendation as one of low strength and to outline in the accompanying narrative the WG’s preferences and judgments that lead to its conclusion. However, if a WG cannot reach a consensus, it may simply highlight controversial areas and outline differences of opinions. The latter approach is also used when there is consensus by majority but also strong dissenting views.

 

Public Review Process

 

An integral part of KDIGO’s guideline development process is internal and external review. An advanced draft of the guideline is reviewed by the KDIGO Board and appointed liaisons from other guideline organizations. The WG incorporates feedback and comments derived from this review into the next version of the draft guideline, which is subsequently submitted for external review. Any interested individual can volunteer to participate in the external public review after registration on the KDIGO website (Reviewer Sign Up ). Comments from stakeholders, including industry representatives, are welcome. In addition, KDIGO specifically invites certain individuals and organizations to participate in this review on the basis of their expertise or interest in the guideline topic or their commitment to guideline development. External reviewers can indicate their degree of agreement with the recommendations and provide general and specific narrative comments. The most recent KDIGO guidelines have elicited more than 100 reviews. Taking these comments into account, the WG develops the final version of the guideline. Each individual recommendation is formally approved by WG members. The final version of the guideline is then submitted for publication.

 

Publication

 

KDIGO guidelines are usually published as a Kidney International Supplement. On occasion, the full guideline or an executive summary will be published in another journal that serves the clinician audience with the most interest in the topic area. For example, the KDIGO guideline on the care of the kidney transplant recipients was published in the American Journal of Transplantation and an Executive Summary containing just the recommendation statements without the evidence tables and rationale sections was published in Kidney International.

All complete Clinical Practice Guidelines and Guideline Executive Summaries are available on the KDIGO website. Translations of the recommendations in six or more languages, prepared with the assistance of WG members and members of the KDIGO Board of Directors and the Board of Councilors, are also posted online. In addition, KDIGO welcomes complete translations of a whole guideline document into different languages by interested volunteers.

 

Dissemination & Implementation

 

The development and publication of a clinical practice guideline are only the first steps in the process to improve patient care. The evidence reviewed for guidelines often originates predominantly in Europe and North America. Thus the practical consequences that can and should be derived from the guideline for patients around the world depend to a large extent on the regional circumstances of health care. For dissemination and implementation of its guidelines, therefore, KDIGO relies heavily on cooperation with other societies and associations. Professional societies are invited to comment on KDIGO guidelines and to specifically address how recommendations may apply in various regions around the world and how they should be prioritized under conditions of restricted resources.

Moreover, KDIGO has formed an Implementation Task Force consisting of six members representing different regions of the world. Task Force members coordinate the work of national and regional representatives of KDIGO to facilitate the presentation and discussion of KDIGO guidelines at national and regional meetings and encourage the publication of translated versions of the guidelines. In addition to the published translations and regional commentaries of guidelines, educational tools, and slide presentations on each guideline are available on the KDIGO website.

Although dissemination is important, the ultimate goal of improving patient outcomes through guideline implementation requires that health care providers are prepared to adjust their practice and that practice according to the guideline recommendations is feasible. The Implementation Task Force will be conducting surveys and clinical studies to evaluate and facilitate guideline implementation.

 

Updating Existing KDIGO Guidelines

 

Recommendations for kidney disease guideline updating: a report by the KDIGO Methods Committee

Guidelines need to be kept up to date to make them credible. The evidence base underlying guidelines is constantly evolving. Occasionally, new findings may require changing a single recommendation or a set of recommendations before a scheduled update of the whole document. Generally, after 5 years, each guideline should be updated, irrespective of whether “significant” new evidence has become available. KDIGO has procedures in place for both intermediate and regular updates.

 

 

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